Subthalamic Single Cell and Oscillatory Neural Dynamics of a Dyskinetic Medicated Patient With Parkinson's Disease.

Musa Ozturk,Sameer A Sheth,Suneel Kumar,Ashwin Viswanathan,Joohi Jimenez-Shahed,Heet Kaku,Nuri F Ince

doi:10.3389/fnins.2020.00391

Abstract

Single cell neuronal activity (SUA) and local field potentials (LFP) in the subthalamic nucleus (STN) of unmedicated Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery have been well-characterized during microelectrode recordings (MER). However, there is limited knowledge about the changes in the firing patterns and oscillations above and within the territories of STN after the intake of dopaminergic medication. Here, for the first time, we report the STN single cell and oscillatory neural dynamics in a medicated patient with idiopathic PD using intraoperative MER. We recorded LFP and SUA with microelectrodes at various depths during bilateral STN-DBS electrode implantation. We isolated 26 neurons in total and observed that tonic and irregular firing patterns of individual neurons predominated throughout the territories of STN. While burst-type firings have been well-characterized in the dorsal territories of STN in unmedicated patients, interestingly, this activity was not observed in our medicated subject. LFP recordings lacked the excessive beta (8–30 Hz) activity, characteristic of the unmedicated state and signal energy was mainly dominated by slow oscillations below 8 Hz. We observed sharp gamma oscillations between 70 and 90 Hz within and above the STN. Despite the presence of a broadband high frequency activity in 200–400 Hz range, no cross-frequency interaction in the form of phase-amplitude coupling was noted between low and high frequency oscillations of LFPs. While our results are in agreement with the previously reported LFP recordings from the DBS lead in medicated PD patients, the sharp gamma peak present throughout the depth recordings and the lack of bursting firings after levodopa intake have not been reported before. The lack of bursting in SUA, the lack of excessive beta activity and cross frequency coupling between HFOs and lower rhythms further validate the link between bursting firing regime of neurons and pathological oscillatory neural activity in PD-STN. Overall, these observations not only validate the existing literature on the PD electrophysiology in healthy/medicated animal models but also provide insights regarding the underlying electro-pathophysiology of levodopa-induced dyskinesias in PD patients through demonstration of multiscale relationships between single cell firings and field potentials.

Highlights

Mapping of the basal ganglia during the implantation of deep brain stimulation (DBS) leads continues to provide researchers insights into the electrophysiology and network dynamics of movement disorders. It is well-known that the structures traversed during intraoperative microelectrode recordings (MER), such as subthalamic nucleus (STN), show distinct patterns both in their spiking (Magariños-Ascone et al, 2000; Rodriguez-Oroz et al, 2001; Starr et al, 2003; Gross et al, 2006; Wong et al, 2009) and oscillatory activity (Wang et al, 2014, 2016; Telkes et al, 2016, 2018) in unmedicated Parkinson’s disease (PD) patients
The prominent increase in the background activity and firing rate in Single cell neuronal activity (SUA) traces were associated with larger signal amplitude in raw local field potentials (LFP) traces (Figure 1D)
Reports on man and non-human primates medicated with apomorphine or levodopa show that population firing rates in the STN did not change with drug intake by itself (Lozano et al, 2000; Levy et al, 2001; Gilmour et al, 2011) but did decrease when dyskinesia was present (Mitchell et al, 1992; Lozano et al, 2000), as it did for our medicated patient

Summary

Introduction

Mapping of the basal ganglia during the implantation of deep brain stimulation (DBS) leads continues to provide researchers insights into the electrophysiology and network dynamics of movement disorders It is well-known that the structures traversed during intraoperative microelectrode recordings (MER), such as subthalamic nucleus (STN), show distinct patterns both in their spiking (Magariños-Ascone et al, 2000; Rodriguez-Oroz et al, 2001; Starr et al, 2003; Gross et al, 2006; Wong et al, 2009) and oscillatory activity (Wang et al, 2014, 2016; Telkes et al, 2016, 2018) in unmedicated Parkinson’s disease (PD) patients. Excessive oscillations discovered in the 8–30 Hz (beta) (Priori et al, 2004; Kühn et al, 2006; Chen et al, 2007; Ray et al, 2008; Eusebio and Brown, 2009) and 200–400 Hz (high frequency oscillations, HFO) bands, and the cross-frequency coupling (CFC) between these bands (Foffani et al, 2003; Lopez-Azcarate et al, 2010; Özkurt et al, 2011; Hirschmann et al, 2016; van Wijk et al, 2017; Telkes et al, 2018; Ozturk et al, 2019), have been shown to correlate with the motor symptoms (van Wijk et al, 2016; Shreve et al, 2017; Ozturk et al, 2019) and subtypes of the disease (Telkes et al, 2018)

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Discussion

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